Rosiglitazone Inhibits Activation of Hepatic Stellate Cells via Up-Regulating Micro-RNA-124-3p to Alleviate Hepatic Fibrosis.
Dig Dis Sci
; 64(6): 1560-1570, 2019 06.
Article
en En
| MEDLINE
| ID: mdl-30673982
BACKGROUND: The activation of hepatic stellate cells (HSCs) is involved in hepatic fibrogenesis and is regulated by the decreased expression of peroxisome proliferator-activated receptor γ (PPARγ). Rosiglitazone (RGZ) is a highly potent agonist of PPARγ. AIMS: To clarify molecular regulatory mechanism of RGZ in the activation of HSCs in hepatic fibrosis. METHODS: A mouse model of hepatic fibrosis was established by carbon tetrachloride with or without RGZ intervention. A vector carrying pcDNA-HOTAIR was constructed and injected into a mouse model. HSCs were isolated from liver tissue and activated by transforming growth factor-ß. The expression of miR-124-3p, HOTAIR, Col1A1, α-SMA, and PPARγ mRNAs was measured by quantitative real-time PCR. The level of PPARγ was measured by Western blotting. The interaction between HOTAIR and PPARγ was assessed by RNA immunoprecipitation (RIP) and RNA pull-down. The target gene of miR-124-3p was determined by luciferase reporter assay and RNA interference approaches. RESULTS: The expression of Col1A1 and α-SMA was reduced after RGZ intervention. Different expressions of HOTAIR and miR-124-3p were observed in liver tissue and HSCs. The luciferase reporter assay and RNA interference approaches indicated that miR-124-3p negatively regulated HOTAIR expression. RIP and RNA pull-down results revealed that PPARγ was interacted by HOTAIR. The therapeutic effect of RGZ on hepatic fibrosis was reversed by overexpression of HOTAIR. CONCLUSIONS: RGZ inhibits the activation of HSCs by up-regulating miR-124-3p. The silencing of HOTAIR by miR-124-3p in HSC activation provided the foundation to understand interactions of ncRNAs and potential treatment target in hepatic fibrosis.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
MicroARNs
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Células Estrelladas Hepáticas
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Enfermedad Hepática Inducida por Sustancias y Drogas
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Rosiglitazona
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Hígado
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Cirrosis Hepática Experimental
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Dig Dis Sci
Año:
2019
Tipo del documento:
Article
Pais de publicación:
Estados Unidos